Novel domain combinations in proteins encoded by chimeric transcripts.
Novel domain combinations in proteins encoded by chimeric transcripts.
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DOI：
10.1093/bioinformatics/bts216
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发表时间：
2012-06-15
期刊：
影响因子：
--
通讯作者：
Valencia A
中科院分区：
文献类型：
--
作者：
Frenkel-Morgenstern M;Valencia A
动机：嵌合RNA转录物通过不同的机制产生，包括前mRNA反式剪接、染色体易位和/或基因融合。最近的研究表明，至少有一些嵌合转录本可以被翻译成功能性嵌合蛋白。结果：为了更好地理解嵌合蛋白的设计原理，我们分析了来自人类的7，424个嵌合RNA。我们专注于这些蛋白质中存在的特定结构域，将它们的排列与已知的人类蛋白质进行比较。我们的方法使用嵌合体的基因组比对，基因-基因连接位点的鉴定和蛋白质结构域的预测。我们发现，嵌合体包含完整的蛋白质结构域显着更经常比随机数据集。具体来说，我们发现，八种不同类型的结构域在所有嵌合体中以及通过RNA-seq实验证实的嵌合体中过度表达。此外，我们发现一些嵌合体可能编码具有新颖和独特结构域组合的蛋白质。鉴于观察到的嵌合体中整个蛋白质结构域的患病率，我们预测，某些假定的嵌合体，缺乏激活结构域可能会积极与他们的父母的蛋白质竞争，从而发挥主导的负面影响。更一般地，嵌合转录物的产生使得可用的蛋白质产物的数量组合增加，这可能干扰亲本基因的功能并影响它们的蛋白质-蛋白质相互作用网络。可用性：我们的脚本可根据要求提供。联系方式：avalencia@cnio.es补充信息：补充数据可从生物信息学在线网站获得。
Motivation: Chimeric RNA transcripts are generated by different mechanisms including pre-mRNA trans-splicing, chromosomal translocations and/or gene fusions. It was shown recently that at least some of chimeric transcripts can be translated into functional chimeric proteins. Results: To gain a better understanding of the design principles underlying chimeric proteins, we have analyzed 7,424 chimeric RNAs from humans. We focused on the specific domains present in these proteins, comparing their permutations with those of known human proteins. Our method uses genomic alignments of the chimeras, identification of the gene–gene junction sites and prediction of the protein domains. We found that chimeras contain complete protein domains significantly more often than in random data sets. Specifically, we show that eight different types of domains are over-represented among all chimeras as well as in those chimeras confirmed by RNA-seq experiments. Moreover, we discovered that some chimeras potentially encode proteins with novel and unique domain combinations. Given the observed prevalence of entire protein domains in chimeras, we predict that certain putative chimeras that lack activation domains may actively compete with their parental proteins, thereby exerting dominant negative effects. More generally, the production of chimeric transcripts enables a combinatorial increase in the number of protein products available, which may disturb the function of parental genes and influence their protein–protein interaction network. Availability: our scripts are available upon request. Contact: avalencia@cnio.es Supplementary information: Supplementary data are available at Bioinformatics online.
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影响因子：
3.3
作者：
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10.1073/pnas.040552697
发表时间：
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